Human norovirus targets enteroendocrine epithelial cells in the small intestine

Abstract

Human noroviruses are a major cause of diarrheal illness, but pathogenesis is poorly understood. Here, we investigate the cellular tropism of norovirus in specimens from four immunocompromised patients. Abundant norovirus antigen and RNA are detected throughout the small intestinal tract in jejunal and ileal tissue from one pediatric intestinal transplant recipient with severe gastroenteritis. Negative-sense viral RNA, a marker of active viral replication, is found predominantly in intestinal epithelial cells, with chromogranin A-positive enteroendocrine cells (EECs) identified as a permissive cell type in this patient. These findings are consistent with the detection of norovirus-positive EECs in the other three immunocompromised patients. Investigation of the signaling pathways induced in EECs that mediate communication between the gut and brain may clarify mechanisms of pathogenesis and lead to the development of in vitro model systems in which to evaluate norovirus vaccines and treatment.

The Role of the Gut Microbiome in Resisting Norovirus Infection as Revealed by a Human Challenge Study

“…Although little is known about HuNoV entry into susceptible target cells, HBGAs act as the attachment receptors to initiate binding of viral particles (10,12). Individuals expressing HBGAs corresponding to the viral pathotype are susceptible to HuNoV infection (6,13), likely facilitating viral access to a different range of target intestinal cells, including enterocytes, macrophages, T cells, B cells, and dendritic cells (5,(14)(15)(16)(17). However, a proportion of people theoretically susceptible to infection (i.e., those expressing the appropriate oligosaccharides) are resistant (6) and/or show no symptoms (18).…”

Hepatitis E virus is an infrequent but potentially serious infection in allogeneic hematopoietic stem cell transplant recipients

“…Although the picture is not specific for norovirus infection 133 , duodenal biopsy may be an important complement to colon biopsy to clarify whether GVHD or norovirus infection seems to be the dominating condition, since norovirus is a pathogen of the small intestine and GVHD might also develop in the upper gastrointestinal tract. In a recent report norovirus antigen and RNA were detected in small bowel biopsies from an immunocompromised patient, using immune histochemistry and in-situ hybridization, respectively 204 . Prospective studies investigating duodenal biopsies in HSCT patients, with and without norovirus infection, and evaluating norovirus antigen and/or RNA detection in tissue, could provide important knowledge and a diagnostic tool in the treatment these patients.…”

Enteric Viral Co-Infections: Pathogenesis and Perspective

“…Indeed, NoV causes ~18% of all cases of diarrhea in outpatient and inpatient settings among all age groups [ 39 ]. NoV has been shown to infect both immune cells and enteroendocrine cells of the small intestinal epithelium in immunocompromised patients [ 40 , 41 ]. Though less widely appreciated as a cause of AGE, sapovirus (SaV) is another member of the Caliciviridae family that causes diarrheal illness similar to NoV, especially in young children and the elderly, and frequently closely follows NoV in prevalence [ 42 , 43 ].…”